4-氯-2′,4′-二甲氧基查尔酮的合成及MDM2蛋白分子对接研究  

Synthesis and molecular docking toward MDM2 protein of 4-chloro-2′,4′-dimethoxychalcone

作　　者：廖波儿 杨争[2] 艾孜提艾力·艾海提 木合布力·阿布力孜[2] LIAO Boer;YANG Zheng;Aizitiaili Aihaiti;Muhebuli Abulizi(Central Laboratory,Xinjiang Medical University,Urumqi 830011,China;School of Pharmacy,Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学中心实验室,乌鲁木齐830011 [2]新疆医科大学药学院,乌鲁木齐830011

出　　处：《新疆医科大学学报》2020年第11期1491-1494,共4页Journal of Xinjiang Medical University

基　　金：国家自然科学基金(81960625)。

摘　　要：目的合成4-氯-2′,4′-二甲氧基查尔酮(化合物I),研究其与鼠双微体蛋白2(MDM2)分子对接的结合能量和位点。方法采用研磨法,以4-氯苯甲醛和2,4-二甲氧基苯乙酮为原料,制备化合物I;通过Autodock软件对化合物I与MDM2蛋白进行分子对接,测定化合物结合能量及结合位点。结果合成目标化合物化合物I,产率为87.21%,经核磁氢谱碳谱表征确定为化合物I。与MDM2分子对接后,结合能量为-7.2 kcal/mol,化合物I与MDM2蛋白中的氨基酸残基Tyr-67和Lys-94的侧链形成CH-π和阳离子-π相互作用。结论化合物I易于合成,产率较高,分子对接展现较好结合能力,对MDM2蛋白具有较强的抑制作用。Objective To synthesize4-chloro-2’, 4’-dimethoxychalcone(Compound I), and to study MDM2 protein binding site and energy.Methods Using grinding method, 4-chloro-2’,4’-dimethoxychalcone was prepared by using4-chlorobenzaldehyde and 2,4-dimethoxyacetophenone as raw materials;the molecular docking of Compound I was performed by Autodock software, and the binding energy and binding site of the compound were measured.Results The target compound I was synthesized with a yield of 87.21%. It was identified as compound I by NMR and H-NMR. After docking with MDM2 molecules, the binding energy is-7.2 kcal/mol. Compound I forms a CH-π and cation-π interaction with the side chains of amino acid residues Tyr-67 and Lys-94 in the MDM2 protein. Conclusion Compound I is easy to synthesizewithhigh yield, better binding abilityofmolecular docking, which has a strong inhibitory effect on MDM2 protein.

关 键 词：查尔酮 合成 MDM2蛋白 分子对接 

分 类 号：R914.5[医药卫生—药物化学]